APPLICANT'S ABSTRACT: Tuberculosis is epidemic among drug users in New York City and elsewhere. Accurate identification of drug users with latent M. tuberculosis infection, to determine eligibility for chemoprophylaxis and thereby to prevent the development of active tuberculosis, is a critical public health goal. This study addresses a number of unanswered questions which currently stand in the way of attaining this goal. Risk factors for M. tuberculosis infection are incompletely understood. Interventions therefore presently cannot be tailored to those at highest risk of infection. In addition, many factors diminish the reliability of drug users' responses to the tuberculin skin test, including HIV infection, poor nutrition, and possibly, drug use itself. Scant data support the current recommendation that a smaller reaction to tuberculin testing in HIV seropositive than in seronegative persons should be accepted as indicative of M. tuberculosis infection. Prospective data are needed to understand the influence of HIV infection, drug use and other related factors on skin test responses and to determine the most appropriate cutpoint for reactions to tuberculin testing for drug users with and with out HIV infection. Cutaneous anergy is considered an indication for chemoprophylaxis for many HIV-seropositive drug users. Yet the risks for and dynamics of this condition are largely uncharacterized, hindering its interpretation in clinical settings. Unanswered questions remain concerning both the toxicity of chemoprophylaxis in drug users at high risk for adverse effects of hepatotoxic medications, and its efficacy. We propose to address these issues by studying prospectively drug users with and without HIV infection currently or formerly enrolled in a substance abuse treatment program (SAP) in the Bronx, NY. Drug users in an ongoing cohort study of HIV infection will be recruited into the TB study. At semiannual research visits, tuberculin and anergy testing will be performed, and interview data regarding risk factors for tuberculosis infection and anergy will be collected. Rates of and risk factors for tuberculin conversion and development of anergy will be defined. The cutpoint most accurately reflecting M. tuberculosis infection in this population will be determined. The incidence of tuberculosis and isoniazed toxicity in patients receiving chemoprophylaxis will be compared to rates in eligible patients not receiving or completing chemoprophylaxis in the SAP's on-site primary care clinic. These data will enhance identification of drug users who are candidates for chemoprophylaxis, and better characterize the risks and benefits of such prophylaxis in this high-risk population.